The present application relates to pharmaceutical formulations and to medical methods of treatment. More particularly, the present invention concerns the use of a compound which acts as a central nervous system sexual response initiator for the normalization of the timing of sexual response in humans and for the prophylaxis or treatment of long-term damage to genital organ.
Proper sexual functioning in men and women depends upon a combination of steps including 1) establishment of the appropriate anticipatory mental set (xe2x80x9cdesirexe2x80x9d), 2) effective vasocongestive arousal (an erection in the male sufficient for vaginal penetration and, in the female, clitoral erection, vaginal engorgement and lubrication), and 3) orgasm. The timing of these steps between partners engaging in sexual relations is mediated by one or more of several compounds which act in neurological pathways in the mesencephalon or mid-brain. These pathways include those termed the serotonergic, dopaminergic, oxytocinergic, and nitroxidergic mid-brain pathways. Timing of the various aspects or parameters of sexual response between partners engaging in sex is important and often mis-matched due to psychological, or sometimes biogenic, dysfunction in one or both of the partners. Even in sex partners having sexual responses deemed to fall within the norm, there is a frequent mis-match of the timing of response.
Orgasm in the male includes the sensation of emission followed by ejaculation. The sensation of emission is one of ejaculatory inevitability and is mediated by contractions of the prostate, seminal vesicles, and urethra. Orgasm in the female is accompanied by contractions of the muscles that line the wall of the outer third of the vagina. In both sexes, generalized muscular tension, perineal contractions and involuntary pelvic thrusting usually occur. Orgasm is followed by resolution, a sense of general relaxation, well-being, and muscular relaxation. During this phase men are physiologically refractory to further erection and orgasm for a variable period of time. In contrast, women may be able to respond to additional stimulation almost immediately.
Sexual response is mediated by a balanced interplay between the sympathetic and parasympathetic nervous systems. Vasocongestion, or erectile tumescence, is largely mediated by parasympathetic (cholinergic) outflow, whereas orgasm is predominantly sympathetic (adrenergic). Ejaculation is almost entirely sympathetic, whereas emission involves a much more finely balanced combination of sympathetic and parasympathetic stimulation.
Normal biological response in humans results in ejaculation typically within about two minutes or more following vaginal penetration. Most women are unable to reach orgasm within this short period of time, one cause of the problem of inappropriate timing of sexual response between sexual partners, even when the sexual responses of both are within physiological norms. In the case of the sexual dysfunction in males known as premature ejaculation, the problem is further exacerbated.
Premature ejaculation in males may have either a psychogenic or biogenic origin in a particular individual, and various treatment methods have been suggested. These include counseling and techniques for learning control of ejaculation and the use of serotonin re-uptake inhibitors such as fluoxetine hydrochloride (Prozac(copyright)) and sertraline hydrochloride (Zoloft(copyright)) to delay the onset of the sensation of emission.
The problem of inappropriate timing of sexual response is not limited to the human species, but occurs also in lower mammals as well, for example, in the breeding of valuable commercial animals such as horses, cattle, sheep, swine and the like and domesticated pets such as dogs and cats.
U.S. Pat. No. 5,770,606 (Ser. No. 08/546,498) discloses a method of ameliorating erectile dysfunction in a male patient by administration of apomorphine or a salt thereof in an amount sufficient to induce an erection adequate for vaginal penetration, but less than that which induces nausea.
The need remains, however, for the development of effective means to normalize the timing of sexual response in mammals, including humans and, in particular, in those cases involving premature ejaculation in human males.
In addition, there is a need for agents for the prophylaxis and treatment of long-term degradative effects or damage to genital organ tissues in mammals.